Despite the approval of multiple CAR T-cell products, access to this therapy remains limited in many developing countries. We conducted a single-arm, open-label, non-randomized, parallel phase 1/2 clinical trial (ClinicalTrials.gov identifier: NCT05333302) at two independent centers: the Vitebsk Regional Clinical Cancer Centre (VRCCC) and the Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology (BRC POHI). The study enrolled patients with relapsed or refractory B-cell malignancies who received an in-house manufactured CD19 CAR T-cell product (BY19) following lymphodepletion with either fludarabine plus cyclophosphamide or cyclophosphamide plus fludarabine and decitabine. Seven patients at VRCCC and sixteen at BRC POHI received CD19 CAR T-cell therapy, comprising 17 patients with B-ALL, one with chronic lymphocytic leukemia (CLL), and five with non-Hodgkin lymphoma. The median age was 45 years (range: 38-56) at VRCCC and 13.5 years (range: 4-30) at BRC POHI. Cytokine release syndrome (CRS) occurred in 18 (67%) of the 27 infusions across both centers, predominantly mild cases. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 12 (44%) patients, with severe ICANS (grade ≥3) in 5 patients (18.5%). The overall response rate (ORR) was 80.0% (16/20), with a complete response (CR) rate of 75.0% (15/20) at the first assessment on day 28. The median progression-free survival (PFS) was 23 months, and the median overall survival (OS) was 55 months. At 12 months, PFS was 83.3% for non-Hodgkin lymphoma patients and 48.3% for B-ALL patients. Higher Cmax levels tended to correlate with better response rates; however, no clear advantage in PFS was observed. In conclusion, our in-house manufactured CD19 CAR T-cell product (BY19) demonstrates a safety and efficacy profile comparable to approved CD19 CAR T-cell therapies. This study underscores the translational potential of localized CAR T-cell manufacturing to expand global access to advanced immunotherapies, especially in middle-income countries. Additionally, incorporating decitabine into the lymphodepletion regimen shows promise in enhancing therapeutic efficacy and warrants further prospective investigation.

The authors have declared no competing interest.

NCT05333302

The work was funded by the State Committee on Science and Technology of Belarus (Agreement No. 201739)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committe of BRC POHI gave ethical approval for this work; Ethics committe of VRCCCg ave ethical approval for this work.

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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All data produced in the present study are available upon reasonable request to the authors